The gut connection: Intestinal permeability as a pathway from breast cancer survivors' relationship satisfaction to inflammation across treatment

Abstract

Background: Breast cancer survivors are prone to weakened gut barriers, allowing bacteria to migrate into the blood stream. Gut permeability fuels inflammation, which, among survivors, can elevate risk for comorbid disease development, cancer recurrence, and a poor quality of life; however, survivors' satisfying relationships can provide health benefits. This longitudinal study used a conceptual model addressing how intimate relationships is associated with health through changes in gut permeability and inflammation.

Method: Breast cancer survivors (n = 139, stages 0-IIIC) completed a baseline visit before treatment and two follow-up visits 6 and 18 months after treatment ended. Women who had an abnormal breast cancer test followed by a benign diagnosis completed visits within a comparable timeframe (noncancer patient controls; n = 69). All women completed questionnaires assessing their relationship satisfaction and provided blood samples to assess two bacterial endotoxin biomarkers, lipopolysaccharide-binding protein (LBP) and soluble CD14 (sCD14), as well as C-reactive protein (CRP) and interleukin 6 (IL-6).

Results: Within-person multilevel mediation analyses showed that when a survivor's relationship satisfaction was higher than usual, her own LBP and LBP/sCD14 were lower, which was associated with lower than her own average CRP and IL-6 (95% CIs [-0.0104, -0.0002]). IL-6 was also higher when older survivors, but not younger survivors, experienced higher than usual intestinal permeability (p = .001). These effects of satisfying relationships held after accounting for cancer-related and behavioral factors. Post-hoc analyses showed LBP, sCD14, and LBP/sCD14 were associated with CRP for the cancer survivors, but only LBP and LBP/sCD14 were linked to CRP among the noncancer control patients.

Conclusion: The gut environment is a new promising candidate for understanding a relationship's long-term health impact, particularly among those with elevated health risks. Survivors may reap multiple physiological benefits from satisfying relationships.

Keywords: Cancer survivors; Gut microbiota; Inflammation; Intestinal permeability; Marriage; Romantic relationships.

Figure 1.

Boxplots of relationship satisfaction scores across the three visits, illustrating that survivors’ satisfaction was higher at the pre-treatment visit compared to the two post-treatment visits. Satisfaction scores range from 0 to 21, and those below 13.5 indicate notable dissatisfaction (Funk and Rogge, 2007).

Figure 2.

LBP=lipopolysaccharide-binding protein. sCD14=soluble CD14. Average estimated marginal means of gut permeability among survivors with notable relationship dissatisfaction and those in satisfying relationships across the study.

Figure 3.

LBP=lipopolysaccharide-binding protein. sCD14=soluble CD14. IL-6=Interleukin-6. Estimated slopes (and standard errors) in IL-6 as a function of survivors’ age and within person (A) LBP, (B), sCD14, and (C) LBP/sCD14. IL-6 data represent back transformed geometric numbers (anti-log10). Slopes are shown for ages 45 (−1SD), 55 (mean), and 65 (+1SD), which also correspond to typical benchmarks across adulthood. *p<0.05; **p<0.01; ***p<0.001.

Figure 4.

LBP=lipopolysaccharide-binding protein. CRP=C-reactive protein. IL-6=Interleukin-6. Coefficients (and standard errors) for the within-person (1-1-1) multilevel mediation models on survivors’ CRP and IL-6. Within-person analyses demonstrate associations among fluctuations in relationship satisfaction, LBP, and inflammation (CRP, IL-6) from visit to visit. *p < 0.05; **p < 0.01; ***p < 0.001